Featured Research

from universities, journals, and other organizations

Jefferson Researchers Crack Rosetta Stone For Tumor Suppressor Protein In Worms

Date:
July 27, 2000
Source:
Jefferson Medical College
Summary:
Uncovering the structure of a "Rosetta Stone" protein may help scientists understand how cells are programmed to die, and in turn, the role loss of the process plays in cancer.

Uncovering the structure of a "Rosetta Stone" protein may help scientists understand how cells are programmed to die, and in turn, the role loss of the process plays in cancer.

Researchers, lead by Charles Brenner, PhD, associate professor of microbiology and immunology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, have determined the 3-dimensional structure of such a Rosetta Stone protein.

First proposed in 1999 by researchers at UCLA, Rosetta Stone proteins occur when two proteins that are separate in some forms of life are fused in another form of life. The fusion "event" almost always reveals a previously hidden interaction between the two nonrelated proteins.

"This may be the first example in cancer biology of separate proteins in one form of life fused in another," says Dr. Brenner, who is a member of Jefferson’s Kimmel Cancer Center. One of the two proteins, Fhit, has been implicated in many common human cancers.

Dr. Brenner and his co-workers report their results July 27 in the journal Current Biology.

Jefferson researchers have been studying the human Fhit protein since 1996. Jefferson Medical College scientists Kay Huebner, PhD, professor of microbiology and immunology and Carlo Croce, MD, professor and chair of microbiology and immunology and director of Jefferson’s Kimmel Cancer Center and their co-workers discovered that the protein is encoded at the most fragile site in the human genome and is lost in many human cancers.

In 1998, Dr. Brenner’s group, working with Drs. Huebner and Croce, determined the 3-dimensional structure of the Fhit protein in its active form. Later in 1998, the same researchers discovered that in the fruitfly Drosophila melanogaster and the flatworm Caenorhabditis elegans, the Fhit protein is naturally fused to an unrelated protein called Nit. Curiously, the NitFhit fusion protein is found in invertebrates, while vertebrates such as humans and mice and fungi such as baker’s yeast contain separate Nit and Fhit proteins. Scientists believe that gene and protein fusions occur because pairs of proteins work in the same biological pathways. In the case of Nit and Fhit, he says, "if you found a Nit and Fhit sequence in the mouse and human, you would have no initial idea that they function in the same pathway," he says. "In finding them as part of the same polypeptide in invertebrates, there’s an indication that they do."

Because the human Fhit protein is inactivated in many human cancers and loss of Fhit leads to cells with defects in programmed cell death, the scientists wanted to discover additional proteins in the Fhit pathway. When they examined the expression of Nit and Fhit in the mouse, they saw both proteins rise and fall in seven of eight tissues almost identically. They also found Nit in every organism in which they had found Fhit. These results made the case for NitFhit as a Rosetta Stone protein very strong.

Dr. Brenner’s team purified the worm NitFhit protein expressed in bacteria, coaxed NitFhit into a crystalline form, and bombarded the crystals with x-rays at Cornell University’s and Brookhaven National Laboratory’s synchrotron sources. Post-doctoral fellow Helen Pace, PhD, working with Dr. Brenner, determined phases of the diffracted X-rays to obtain a three-dimensional map of the NitFhit protein.

"The structure clearly shows how Nit interacts with Fhit," he says. "A central Nit tetramer binds a Fhit dimer on one side of the molecule and another Fhit dimer on the other side of the molecule. Specific Nit sequences invade Fhit sequences to make Nit fit."

The Jefferson scientists are particularly encouraged that the flatworm is a leading system in which to study cell death. According to Dr. Brenner, the structure of NitFhit tells us that Fhit is functioning in a large complex with Nit in the worm. Following the activity of Nit in worms and other organisms "ought to take us to the next vista point.

"This structure is leading us to the idea that regulation of Nit may be important for the cell death activity of Fhit."

Jefferson researchers are beginning to investigate the role of Nit and Fhit in the development of other organisms, such as zebrafish, which have separate proteins. They would also like to determine a potential role of NitFhit in cell death in the developing worm.

Dr. Brenner notes that Fhit is absent in tumors and is not a cancer drug target. "If Nit is a pro-survival enzyme, which ought to be inhibited by Fhit, then Nit itself may be the drug target."


Story Source:

The above story is based on materials provided by Jefferson Medical College. Note: Materials may be edited for content and length.


Cite This Page:

Jefferson Medical College. "Jefferson Researchers Crack Rosetta Stone For Tumor Suppressor Protein In Worms." ScienceDaily. ScienceDaily, 27 July 2000. <www.sciencedaily.com/releases/2000/07/000727081405.htm>.
Jefferson Medical College. (2000, July 27). Jefferson Researchers Crack Rosetta Stone For Tumor Suppressor Protein In Worms. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2000/07/000727081405.htm
Jefferson Medical College. "Jefferson Researchers Crack Rosetta Stone For Tumor Suppressor Protein In Worms." ScienceDaily. www.sciencedaily.com/releases/2000/07/000727081405.htm (accessed September 2, 2014).

Share This



More Health & Medicine News

Tuesday, September 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Snack Attack: Study Says Action Movies Make You Snack More

Snack Attack: Study Says Action Movies Make You Snack More

Newsy (Sep. 2, 2014) You're more likely to gain weight while watching action flicks than you are watching other types of programming, says a new study published in JAMA. Video provided by Newsy
Powered by NewsLook.com
U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

Newsy (Sep. 2, 2014) The U.N. says the problem is two-fold — quarantine zones and travel restrictions are limiting the movement of both people and food. Video provided by Newsy
Powered by NewsLook.com
Doctors Fear They're Losing Battle Against Ebola

Doctors Fear They're Losing Battle Against Ebola

AP (Sep. 2, 2014) As a third American missionary is confirmed to have contracted Ebola in Liberia, doctors on the ground in West Africa fear they're losing the battle against the outbreak. (Sept. 2) Video provided by AP
Powered by NewsLook.com
Tech Giants Bet on 3D Headsets for Gaming, Healthcare

Tech Giants Bet on 3D Headsets for Gaming, Healthcare

AFP (Sep. 2, 2014) When Facebook acquired the virtual reality hardware developer Oculus VR in March for $2 billion, CEO Mark Zuckerberg hailed the firm's technology as "a new communication platform." Duration: 02:24 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins